Treatment algorithm for iMCD. iMCD patients should be stratified for disease severity per Figure 1. For nonsevere iMCD, siltuximab is recommended as frontline therapy for patients with nonsevere iMCD. Tocilizumab can be used if siltuximab is not available or approved. Steroids are useful adjunctive therapy, and the dose can be tailored according to the severity of the disease. Patients responding to anti–IL-6 mAb therapy should be continued indefinitely. *For patients with mild symptomatology, a limited course of rituximab is an alternative option. Patients not responding to anti–IL-6 mAb therapy should be considered for rituximab-based therapy + steroids ± immunomodulatory/immunosuppressive agents. ♠Immunomodulatory/immunosuppressive agents for second- or third-line therapy include thalidomide, cyclosporine A, sirolimus, anakinra, or bortezomib, but we recommend consulting with an expert at this stage. For severe iMCD, severe disease must be closely monitored, as life-threatening events may occur in this population. Severely ill patients should be treated with siltuximab and high-dose steroids, but if no clear response occurs within 1 week (or if status worsens at any time), then combination chemotherapy should be considered. When possible, expert advice should be sought to identify the most appropriate therapy for a given patient. Further therapy is best individualized. †Examples of chemotherapy include R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), R-VDT-PACE (rituximab, bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide), or etoposide/ cyclophosphamide/rituximab. Siltuximab is the preferred anti–IL-6 therapy. However, in countries where siltuximab is not available or approved, tocilizumab can be used instead. Supporting evidence category 1, green boxes; category 2A, yellow boxes; category 2B, blue boxes. CTC, common toxicity criteria.